PROJECT SUMMARY/ABSTRACT- Clinical Science Research Core: The Clinical Science Research Core (CSRC) enhances and facilitates nutrition/obesity-related clinical and translational research by assisting investigators in conducting studies in human subjects through the operation of two sub-cores. The Clinical Studies Performance sub-core facilitates clinical research by assistance with: i) subject recruitment, ii) planning and performance of clinical studies (i.e., a diverse array of tracer and non- tracer protocols such as the hyperinsulinemic-euglycemic clamp procedure, multi-tracer meal tests, intravenous and oral glucose tolerance tests, and arterial venous balance studies, to assess substrate and insulin kinetics), iii) body composition assessments [by using dual energy X-ray absorptiometry (DEXA), BodPod, Peapod, magnetic resonance imaging (MRI), and magnetic resonance spectroscopy (MRS)], iv) mixing of intravenous tracer and hormone solutions, v) acquisition of tissue (adipose, muscle, intestine) biopsy samples, vi) exercise (endurance and strength) and physical performance testing, vii) indirect calorimetry, viii) lifestyle (diet manipulation, behavioral therapy, exercise training, and weight loss/weight gain) interventions, ix) ingestive behavior (taste perception and preference) testing, and x) cardiovascular assessments (e.g., echocardiography, endothelial function, carotid artery intima-media thickness). The Metabolic Kinetics sub- core provides comprehensive services and training to study diverse areas of metabolic function, including: i) design of tracer and non-tracer protocols to evaluate in vivo substrate kinetics (e.g. glucose and fatty acid flux, VLDL-triglyceride secretion rate), insulin sensitivity, insulin secretion rates, and -cell function, ii) sample processing and measurement of stable isotope enrichment of metabolic substrates in blood, tissue, and primary human tissue culture samples, and iii) mathematical modeling of tracer and non-tracer data for the assessment of metabolic kinetics, insulin sensitivity, insulin secretion rates, and -cell function. In addition, the CSRC provides training for investigators, their staff, and research fellows in these areas of clinical research, both in the form of one-on-one hands-on instruction as well as through seminars and lecture series. Combining these services within one Core provides a cohesive organizational structure that facilitates the performance of complex clinical research studies, fosters interdisciplinary collaborations between NORC investigators, and reduces the barriers for basic scientists, and non-physician and young investigators who wish to conduct clinical research. The CSRC also ensures that all studies and procedures that are supported by the core are conducted in compliance with federal and local (state and hospital) regulations regarding research involving human subjects.